TY - JOUR
T1 - Sphingolipids in Alzheimer's disease, how can we target them?
AU - Crivelli, Simone M
AU - Giovagnoni, Caterina
AU - Visseren, Lars
AU - Scheithauer, Anna-Lena
AU - de Wit, Nienke
AU - den Hoedt, Sandra
AU - Losen, Mario
AU - Mulder, Monique T
AU - Walter, Jochen
AU - de Vries, Helga E
AU - Bieberich, Erhard
AU - Martinez-Martinez, Pilar
N1 - Copyright © 2020 Elsevier B.V. All rights reserved.
PY - 2020/1
Y1 - 2020/1
N2 - Altered levels of sphingolipids and their metabolites in the brain, and the related downstream effects on neuronal homeostasis and the immune system, provide a framework for understanding mechanisms in neurodegenerative disorders and for developing new intervention strategies. In this review we will discuss: the metabolites of sphingolipids that function as second messengers; and functional aberrations of the pathway resulting in Alzheimer's disease (AD) pathophysiology. Focusing on the central product of the sphingolipid pathway ceramide, we describ approaches to pharmacologically decrease ceramide levels in the brain and we argue on how the sphingolipid pathway may represent a new framework for developing novel intervention strategies in AD. We also highlight the possible use of clinical and non-clinical drugs to modulate the sphingolipid pathway and sphingolipid-related biological cascades.
AB - Altered levels of sphingolipids and their metabolites in the brain, and the related downstream effects on neuronal homeostasis and the immune system, provide a framework for understanding mechanisms in neurodegenerative disorders and for developing new intervention strategies. In this review we will discuss: the metabolites of sphingolipids that function as second messengers; and functional aberrations of the pathway resulting in Alzheimer's disease (AD) pathophysiology. Focusing on the central product of the sphingolipid pathway ceramide, we describ approaches to pharmacologically decrease ceramide levels in the brain and we argue on how the sphingolipid pathway may represent a new framework for developing novel intervention strategies in AD. We also highlight the possible use of clinical and non-clinical drugs to modulate the sphingolipid pathway and sphingolipid-related biological cascades.
KW - Alzheimer's disease
KW - Blood brain barrier (BBB)
KW - Ceramide
KW - Fingolimod (FTY720)
KW - GW4869
KW - Sphingomyelin (SM)
KW - Sphingosine-1-phosphate (S1P)
KW - Tricyclic dibenzoazepines (TCA)
UR - http://www.scopus.com/inward/record.url?scp=85078209948&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.addr.2019.12.003
DO - https://doi.org/10.1016/j.addr.2019.12.003
M3 - Review article
C2 - 31911096
SN - 0169-409X
VL - 159
SP - 214
EP - 231
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
ER -